ASEPTIC PROCESSING: ONE - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 229

considering what a planned aseptic processing might look like and what are the
consequences of design choices from a risk perspective. Using both the inter-
vention risk and processing technology components together affords the most
comprehensive use of the A-A method.
The Parenteral Drug Association developed a technical report on risk assess-
ment for aseptic processing that utilized an FMEA-type approach [31]. The use
of an FMEA type approach in this effort is inherently limiting, in that many of
the nuances and choices associated with aseptic processing cannot be considered
with precision. In some ways, this effort merely codifies the thinking that industry
went through during the years of greatest improvement in aseptic processing. Its
overall utility is rather limited compared to the more evolved methods described
previously.
Warren Charlton developed a quantitative risk evaluation method of extraordi-
nary simplicity [32]. This method follows a classical FMEA type approach with
severity, frequency, and detectability rankings, but incorporates a defined risk
value above which change to the process design is expected. This method makes
a strong case for consideration of design elements across the process to provide
greater confidence in the acceptability of the outcome.
The inclusion of a definitive limit in risk assessment that would drive process
improvement is inherently desirable; however, where that line should be drawn
is of course open to discussion. Most of the above cited risk models include
subjective assessments of the contributing elements to aseptic risk. Given that
subjectivity, the utility of a defined limit can be questioned. The key questions
relative to a defined expectation are as follows:
• Would that defined limit be suitable in all process situations?
• What would constitute “proof” of the acceptability of a specific limit?
• Is the method of “proof” broadly applicable?
These questions and others like them will likely remain unanswered for some
time.
An evaluation of several different risk models for aseptic processing was con-
ducted by Katayama et al. based on operations at several operating facilities
in Japan [33]. This article highlighted the difficulties in using microbial mon-
itoring and media fill results as means for discerning differences in perceived
performance of the facilities. As a result of this belief, they expressed prefer-
ence for the A-A method; however, that may be an artifact of the facilities
involved in the comparison and not an indication of the true superiority of that
method.
The importance of aseptic processing is such that there are likely to be
continued efforts to develop improved risk assessment methods. Anything that
contributes positively to understanding and potentially alleviating the inherent
contamination hazards with aseptical processing should be considered as a means
to reduce the associated risk.